Forward viewing catheter-delivered microbubble enhanced sonothrombolysis (FV-CAMUS) Deep vein thrombosis (DVT) induced pulmonary embolism (PE) causes more than 0.1 million deaths annually in the US alone. Recent innovative treatment techniques for thrombolysis, such as pharmacological dissolution or fibrinolysis and mechanical fragmentation, have showed progressive results, yet still suffer from severe limitations such as low thrombolysis efficiency and long treatment times, frequent bleeding complications, high failure rate, vein injury associated with severe regional dysfunction, recurrence, and the relatively large particle size of residual clot debris which can result in distal embolism. This has led to great interest in sonothrombolysis, the use of focused ultrasound to disrupt clots, yet current commercial sonothrombolysis systems (e.g. EKOS) are still limited by long treatment times and peripheral tissue damage due to heating and excessive acoustic exposure. More recently, our group and others have demonstrated several advances which promise to improve the performance (significantly reduced treatment time) and safety of thrombolysis using a microbubble-mediated forward-looking dual frequency catheter based technology. We hypothesize that the development of a new approach for catheter sonothrombolysis combining multi-frequency tools as well as cavitation-enhancing agents can substantially improve the efficacy, safety, and impact of this approach. In this project, we develop innovative technologies from our collaborative group, each of which has shown notable advantages over current technology, and we hypothesize that together they can overcome existing challenges in the aforementioned acute embolism treatments. Specifically, a 4-French catheter will be integrated with dual acoustic sources - a small aperture dual frequency forward-looking ultrasound transducer, combined with a micro-tube for delivery of microbubbles and lytic agent (tissue-type plasminogen activator or t-PA), to achieve Forward Viewing CAtheter- delivered MicrobUbble enhanced Sonothrombolysis (FV-CAMUS). The FV-CAMUS catheter will be designed, prototyped and characterized, followed by in-vitro, ex-vivo and in-vivo thrombolysis tests in large animals. The proposed FV-CAMUS technology will provide a new tool enabling accurate, fast, and safe thrombus treatment.